Increasing evidence supports that 5HTTLPR polymorphism of the serotonin transporter gene(5HTTLPR) might associate to bipolar disorder and affective temperaments as measured by TEMPS-A. But the results are discrepant, furthermore, there are no data from Chinese population.

The present study was designed to investigate association between 5HTTLPR and bipolar disorder and affective temperaments of patients with bipolar disorder in the specific Chinese population and add new evidence to the field.

There hundred and five patients with bipolar disorder and 272 normal controls were included in the present case-control study⌧Temperament Evaluation of Memphis, Pisa, Paris and San Diego -autoquestionnaire version (TEMPS-A) in Chinese was used to assess affective temperament. Chi-square test, T test, Nonparametric test and ANOVA were employed to explore association between 5HTTLPR polymorphism and bipolar disorder and affective temperament of patients with bipolar disorder.

5-HTTLPR L/S polymorphism was associated with bipolar disorder in female (genotype χ2 = 6.769⌧P = 0.034⌧allele χ2 = 6.028⌧P = 0.014) and the S allele was associated with anxious temperament (t = 8.248⌧P = 0.005) in patients with bipolar disorder. the LA allele of 5-HTTLPR rs25531 A/G polymorphism was associated with hyperthymic temperament in patients with bipolar disorder (Z = −2.205⌧P = 0.027).

5-HTTLPR might have an effect on the prevalence of bipolar disorder in female and regulate affective temperaments of patients with bipolar disorder in some degree in Chinese population.

rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS. In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.

Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.

Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.

Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.

rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS.

In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.

Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.

Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.

Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.

Bioinformatic investigations indicate that has-mir-206 (microRNA-206, miRNA-206) could regulate BDNF protein synthesis by interfering with BDNF mRNA translation, which is disrupted in bipolar disorder (BPD).

This study is to investigate whether miRNA-206 gene variants were associated with BPD susceptibility in a Han Chinese population.

342 patients who met DSM-IV criteria for bipolar disorder type I (BPD-I) or type II (BPD-II) and 386 matched health controls were enrolled into this study. the miRNA-206 gene and +/-500bp were selected for gene sequencing. for the case-control genetic comparisons, differences in the genotype and allele distributions between patients and controls were examined using Pearson's χ2 test.

Gene sequencing showed that there are two polymorphisms rs16882131(C/T) and rs62408583 (A/C) located at the upstream of miRNA-206 gene, which are complete linkage disequilibrium. the association analysis showed that there was no significant difference for genotype frequencies (χ2 = 2.075, df = 2, P = 0.354) or for allele frequencies (χ2 = 0.041, df = 1, P = 0.839) between BPD patients and controls. Similarly, no significant difference was found between BPD-I patients and controls (genotype χ2 = 1.411, df = 2, P = 0.494; allele χ2 = 0.380, df = 1, P = 0.538). However, there was significant difference between BPD-II patients and controls (genotype χ2 = 7.933, df = 2, P = 0.019; allele χ2 = 5.403, df = 1, P = 0.020).

Our findings do not support that BPD susceptibility was associated with miRNA-206 gene polymorphisms in the studied Han Chinese population. the association between miRNA-206 gene polymorphisms and bipolar disorder type II is needed to be carefully interpreted. Further studies are necessary to elucidate the involvement miRNA-206 in the pathophysiology of BPD.

To explore the difference in the clinical features between bipolar disorder and unipolar depression from the clinical phenomenology.

Two hundred bipolar patients with their current depressive episode and five hundred and sixty three recurrent depression were involved in the study. Clinical features of these two groups were compared and stepwise Logistic regression was used to identify the relationship between clinical features and bipolar disorder.

Clinical features of depressive episode which was different between two groups and were associated with bipolar disorder were as follows: age at onset of bipolar was earlier than that of unipolar depression; Bipolar patients whose age at onset before 25 years were more than unipolar depression; Sexual appetites which was one of atypical depressive symptoms were more common in bipolar depression than in unipolar depression; with psychiatric symptoms, psychomotor retardation, mood instability and duration of every depressive episode < 3 months, were more common in bipolar depression group than in unipolar depression group; Cognitive impairment factor, one of factors of HAMD-17 score, was significantly higher in bipolar depression group than in unipolar depression group. The odd ratio were 1.54, 1.50, 3.25, 1.99, 1.89, 1.48, 1.63, 1.63, and 1.42 separately.

The founding suggested that unipolar depression and bipolar depression might be distinct disorder, and age at onset, age at onset < 25, sexual appetites, psychiatric symptoms, psychomotor retardation, mood instability and duration of every depressive episode < 3 months might be potential to be the predictors of bipolar disorder.

To explore the factors associated with occurrence of suicidal risk after treatment of SSRI in bipolar disorder with their first depressive episode.

One hundred and seventy seven bipolar patients were enrolled in this retrospective study. One hundred fifty four patients were included in non-occurrence of suicidal risk group, while twenty three were included in occurrence of suicidal risk group. To compare the demographic and clinic features between these two groups. Stepwise Logistic regression model was used to identify the associated factors. Concordance statistics (i.e. the area under the ROC curve) was used to compute the discrimination of the associated factors, and Hosmer-Lemeshow goodness-of-fit statistic was used to measure the goodness-of-fit.

Clinical features associated with occurrence of suicidal risk after treatment of SSRI in bipolar disorder were as follows: psychotic symptom and symptom of irritability. The odd ratio was 6.23 and 4.04 separately.

This study demonstrated indicated that psychotic symptom and symptom of irritability were associated with occurrence of suicidal risk after treatment of SSRI in bipolar disorder, and it suggested that these two symptoms might be potential to be the predictors of occurrence of suicidal risk after treatment of SSRI in bipolar disorder.

Major depressive disorder (MDD) is associated with abnormal functional connectivity (FC) of amygdala and decreased function of cortico-limibic circuit, which play important roles in the pathogenesis of MDD. However, little is known about the connectivity alterations in late-onset depression (LOD), and whether such disrupted function is correlated with cognitive impairment is unclear.

A total of twenty-three LOD patients and thirty-seven controls underwent neuropsychological tests and resting-state functional magnetic resonance imaging (RS-fMRI). Regional homogeneity (ReHo) and FC of bilateral amygdala seed were used to analyze blood oxygen level-dependent fMRI data between groups.

Compared to controls, LOD groups showed weaker functional activity in bilateral middle frontal gyrus and left medial orbitofrontal gyrus, moreover, the decreased ReHo was positively correlated with Trail making test-B score (TMTB, r= 0.462,P= 0.04). In aspects of FC, left amygdala has reduced FC with right fusiform gyrus, right superior temporal gyrus and right putamen, while right amygdala has reduced FC with left cerebellum. Further correlative analysis found that the decreased FC between amygdala and right putamen was positively correlated with Verbal fluency test-verb score (VFT-verb, r= 0.513,P= 0.021) and the decreased FC between amygdala and superior temporal gyrus was positively correlated with Auditory Verbal Memory Test-delayed recall score (AVLT-delayed recall, r= 0.446,P= 0.049).

Our finding of reduced activation of prefrontal gyrus as well as decreased connection of bilateral amygdala may be key factors of impaired cognitive function in LOD patients and these changes could be early indicator for cognitive deficits.

The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among patients with SSD, major depressive disorder (MDD) and healthy controls.

Gene expression profiling was conducted in peripheral blood leucocytes from drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group) using global mRNA expression arrays. Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step.

We identified SSD and MDD gene signatures from blood-based gene expression profile and build a SSD- MDD disorder model with higher predictive power. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P <= 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy.

Blood cell-derived RNA may have significant value for performing diagnostic functions and identifying disease biomarkers in SSD and MDD. These 48 gene model could classify SSD, MDD, and healthy controls.

To study the relationship between insulin-like growth factor 1 receptor (IGF1R)and subsyndromal symptomatic depression (SSD).

In this case-control study, real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) with TaqMan MGB was used to analyzing the differences of IGF1R gene mRNA expression in peripheral leukocytes between subsyndromal symptomatic depression group(n = 47) and healthy controls(n = 52). At the same time Hamilton Depression Rating Scale -17(HAMD17) were assessed.

IGF1R gene mRNA expression was 0.21 ± 0.11 in SSD group, 0.56 ± 0.37 in healthy group, and there was significant difference between both groups on IGF1R expression(z = 39.54, P < 0.001). the expression levels of IGF1R in SSD patients was not correlated with Hamilton score(r = −0.292, p = 0.275).

This study suggested that the decreased expression of IGF1R were related with the pathophysiology of SSD.

Epigenetic changes may play a role in the etiology of psychotic diseases. It has been demonstrated that olig2 is implicated in schizophrenia (SCZ) and bipolar disorder (BPD). the aim of this study was to investigate the methylation status of a promoter region of the olig2 gene in BPD and SCZ patients.

Our study included 41 BPD and 45 SCZ (DSM-IV criteria) as well as 53 control subjects. DNA was extracted from blood leukocytes and bisulfited sequence analysis was used to determine the DNA methylation status of a typical CpGs island within the promoter region of olig2.

We found the methylated cytosines occurred mainly in two clusters. Olig2 gene promoter was hyper-methylated(∼30%) in DNA derived from the blood leukocytes in SCZ and BD compared to the controls subjects(P = 0.01 and P = 0.03, respectively). There was no statistically significant difference in frequency of site-specific cytosine methylation modification of Olig2 gene between SCZ patients and BD patients(P = 0.21).

We observed increased DNA methylation in the promoter region of the olig2 gene of SCZ and BPD. This could explain the reported decrease of the gene expression. the current study supports the growing interest of DNA methylation in psychopathology.

The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.

Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.

We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).

Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.

The potential pattern of regional cerebral blood flow (rCBF) in major depressive disorder (MDD) underlies different response to antidepressants medication remain unclear. This study aimed to investigate the differences of rCBF between patients with different treatment response.

Eighty MDD patients [(44 treatment-responsive depression (RD) and 36 non-responding depression (NRD)] and 42 healthy controls (HC) underwent pulsed arterial spin labeling (PASL) scans in magnetic resonance imaging and clinical estimates. The exact rCBF values of each groups were obtained via quantification evaluation.

Compared to NRD, the RD patients showed decreased rCBF values in frontal sensorimotor network (i.e. left paracentral lobule, left medial frontal gyrus, right superior frontal gyrus and right middle frontal gyrus), and further receiver operating curve (ROC) analyses demonstrated that the altered rCBF in these four regions exhibited outstanding performance on distinguishing NRD from RD. The NRD also exhibited reduced rCBF in bilateral cerebellum posterior lobe and right middle occipital gyrus and elevated rCBF in right postcentral gyrus and right middle frontal gyrus as compared to HC.

The decreased rCBF in frontal sensorimotor network appeared to be distinct characteristics for NRD, and might be severed as promising neuroimaging markers to differentiate depressed patients with weak early response to antidepressant medication. These findings expand our understanding of neural substrate underlying the antidepressant efficacy.

The authors have not supplied their declaration of competing interest.

The intuitive association between cognitive dysfunction in late onset depression (LOD) and the aberrant functional activity in the brain's default-mode network (DMN) has prompted interest in exploring the role of the DMN in LOD. The altered pattern of resting state voxel-mirrored homotopic connectivity (VMHC) in cognitive processes is not yet well understood in LOD.

The study was designed to examine the implicit coupling between the alteration of interhemispheric functional coordination and cognitive impairment in LOD. Thirty-one LOD patients and 37 matched healthy controls (HC) underwent neuropsychological tests and functional magnetic resonance imaging (fMRI) in this study.

Compared to HC group, attenuated VMHC in superior frontal gyrus, superior temporal gyrus, posterior cerebellar lobe, postcentral and precentral gyrus was observed in LOD. Neuro-behavioral relevancy approach revealed that the imbalanced interhemispheric functional coordination in bilateral cerebellum was positively correlated with the performance of trail making test in LOD (r = 0.367, P = 0.040).

Altered linkage pattern of intrinsic homotopic connectivity and cognition was firstly investigated in LOD, and it would provide a novel clue to reveal the neural substrates underlying the cognitive dysfunction in LOD.

The authors have not supplied their declaration of competing interest.

The diagnosis of major depressive disorder (MDD) is symptom based due to the lack of biological biomarker. p11 protein was recently found to be an important factor mediating depression-like states and antidepressant responses. The aim of the study was to assess whether p11 protein in urine can serve as a potential biomarker for major depression, and the relationship of its levels among urine, serum and cerebrospinal fluid (CSF).

We obtained urine samples from 13 drug-free MDD patients and 13 age- and gender-matched healthy controls. We also collected urine, serum and cerebrospinal fluid samples from 13 of fracture patients or cesarean section patients in the spinal anesthesia. The concentrations of p11 protein were measured using ELISA.

In MDD patients, urine levels of p11 protein were all less than the minimum detectable concentration of the ELISA kit. The urine levels of p11 were detectable only in one healthy control. In the spinal anesthesia patients, we can detect p11 concentrations in both serum and urine in only two patients. Besides, levels of p11 were detectable in the serum of one patient and urine of another patient. We were unable to measure CSF levels of p11 in all patients.

Concentrations of p11 protein in the body fluids are very low and unstable. The sensitivity of the current p11 ELISA kit is currently unsatisfactory, requiring the development of an ELISA kit of higher sensitivity to determine whether p11 in body fluids can serve as biomarker for depression.

The authors have not supplied their declaration of competing interest.

Psychomotor retardation (PMR) in depression is analogous to the hypokinesia in Parkinson's disease, which is associated with the unbalanced direct and indirect pathways of cortico-basal ganglia-thalamo-cortical (CBTC) circuitry. This study hypothesized PMR in major depressive disorder (MDD) should be associated with the hyperactivity of CBTC indirect pathways.

To substantiate the hypothesis that the PMR symptom of MDD might attribute to the hyperactivity of the ortico-basal ganglia-thalamo-cortical indirect pathway which could inhibit psychomotor performance.

We investigated the intrinsic stiato-subthalamic nucleus (STN)-thalamic functional connectivity (FC), three pivotal hubs of the indirect pathway, in 30 MDD patients with PMR (PMR group) and well matched 30 patients without PMR (NPMR group) at baseline, and 11 patients of each group at follow-up who remitted after antidepressant treatment.

The results showed increased STN-striatum FC of PMR group at baseline and no more discrepancy at follow-up, and significant correlation between PMR severity and thalamo-STN FC.

Our findings suggested the increased STN- striatum FC should be considered as a state biomarker to distinguish MDD patients with PMR from patients without PMR at acute period, and thalamo-STN FC could be identified as the predictor of the PMR severity for MDD patients.

The authors have not supplied their declaration of competing interest.

Emerging evidences indicate that the alteration of interhemispheric functional coordination may be involved in the pathogenesis of major depressive disorder (MDD). In present study, we aim to explore the potential marker by using the voxel-mirrored homotopic connectivity (VMHC) approach, which may be contributing to predict the clinical prognosis in MDD.

Eighty-two MDD patients and 50 normal control (NC) subjects participated in this study. We divided the MDD group into unremitted and remitted group according to the reduction rate of Hamilton Rating Scale for Depression (HAMD) within 2 weeks.

The study detected significantly decreased VMHC in bilateral precuneus (pCu), inferior temporal gyrus (ITG) and increased VMHC in middle frontal gyrus (MFG) and caudate nucleus when compared remitted depression (RD) group to unremitted depression (URD) group. Meanwhile, when compared with NC group, the URD group presented reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral gyrus. Furthermore, the VHMC in media frontal gyrus, postcentral gyrus and precentral gyrus were significantly decreased in RD group. Correlation analysis suggested that reduced VMHC in bilateral pCu was negatively correlated with the baseline HAMD score of URD (r = −0.325, P = 0.041). Receiver operating characteristic (ROC) curve indicated that three regional VMHC changes could identify depressed patient with poorer treatment response: ITG [area under curve (AUC) = 0.699, P = 0.002, 95% CI = 0.586–0.812], MFG (AUC = 0.692, P = 0.003, 95% CI = 0.580–0.805), pCu (AUC = 0.714, P = 0.001, 95% CI = 0.603–0.825).

The current study combined with previous evidence indicates that the subdued intrinsic interhemispheric functional connectivity might represents a novel neural trait involved in the pathophysiology of MDD.

The authors have not supplied their declaration of competing interest.

Several lines of evidence implicate dopamine is involved in the psychomotor retardation (PMR) in major depressive disorder (MDD). Besides, abnormal cerebral blood flow (CBF) of PMR was also found in the cortico-basal ganglia-thalamo-cortical (CBTC) circuitry. We hypothesize that the polymorphisms of the dopaminergic pathway should be associated the abnormal CBF in the CBTC circuitry.

To investigate the association of the polymorphisms throughout the dopaminergic pathway with the cerebral blood flow (CBF) of PMR in MDD.

The blood sample of 63 patients (23 PMR, 40 NPMR) were collected for genotyping the dopaminergic polymorphisms (92 SNPs from10 genes). After quality controlling, 15 SNPs in 8 candidate genes were entered into the mass univariate modeling analysis. For the statistical analysis, patients with unqualified fMRI image and unmatched demographic data were ruled out. Consequently 56 patients (23 PMR, 33 NPMR) were taken into the statistical analysis.

Genotype-by PMR associations with the CBF differences predominately distributed in bilateral prefrontal cortex (PFC), temporal cortex, and striatum, the left thalamus, the right primary motor cortex, insular cortex, fusiform gyri, and lingual gyri. There were significant negative correlation between the CBF of the PFC and the PMR severity. However, the CBF of the striatum and the thalamus were positively correlated with the PMR severity.

The polymorphisms of dopaminergic pathway are associated with not only CSTC circuitry, but also some other brain regions involving in cognition and emotion controlling. While the increased CBF of PFC might suppress PMR, the increased CBF of striatum and thalamus adversely aggravate PMR.